Quantitative analysis of memantine in human plasma by gas chromatography/negative ion chemical ionization/mass spectrometry

A sensitive and specific method for the determination of memantine in human plasma is presented. Memantine was extracted from plasma and derivatized to the pentafluorobenzoyl derivative in a one‐step procedure avoiding any sample concentration steps. Adamantine was used as an internal standard. The compounds were measured by gas chromatography/negative ion chemical ionization mass spectrometry without any further processing. Using this detection mode, the fragment ions at m / z 353 and 325 were obtained at high relative abundance. Calibration graphs were linear over the range 0.117–30 ng ml −1 . At the limit of quantification (LOQ), the inter‐assay precision was 2.00% and the intra‐assay variability was 3.22%. The accuracy at the LOQ showed deviations of −1.42% (intra‐assay) and −2.47% (inter‐assay). The method is rugged, rapid and robust and was applied to the batch determination of memantine during pharmacokinetic profiling of the drug. Copyright © 2002 John Wiley & Sons, Ltd.